Donald C. Dyer

In vitro release of prostaglandins from the renal medulla

Abstract Prostaglandins E 2 and F 2α were released from slices of rabbit renal inner incubated in vitro in Krebs solution. Since the amounts released spontaneously were greater than those directly extractable from non-incubated tissues and were temperature- and oxygen-dependent, it was concluded that some of the released prostaglandins had been newly synthesized. Phospholipase A stimulated the rate of release while depolarization with potassium or incubation in the presence of norepinephrine or isoproterenol were without demonstrable effects. Vasopressin (100 mU/ml) significantly increased the release of prostaglandins. This effect by vasopressin was apparently independent of changes in cyclic AMP levels since dibutyryl cyclic AMP reduced the release of prostaglandins below control levels. The enhanced release of prostaglandins by vasopressin supports the hypothesis that prostaglandins may play a role in the regulation of hormonal effects in the kidney.

Autonomic receptors in isolated rainbow trout vasculature

Pre-gill arterial vessels (bulbus arteriosus and ventral aorta) from rainbow trout were easily excised, helically cut, and investigated; whereas, post-gill arterial and venous vessels were either too small or too enmeshed with connective tissue to permit study. Atropine shifted dose-response curves to acetylcholine in the bulbuss arteriousu and ventral aorta to the right. Responses to acetylcholine in the bulbus arteriosus were not antagonized by hexamethonium and tubocurarine. Physostigmine (10−7 M) and diisopropylfluorphosphate (10−4 M) did not alter responses to acetyl-choline in bulbus arteriosus. Contractions to pilocarpine were blocked by atropine. Contractile responses to epinephrine were antagonized by phentolamine, were potentiated by propranolol, and were not altered by cocaine. The potentiation of epinephrine by propranolol was greater in ventral aortic tissue located proximal to the heart. Relaxations of acetylcholine-induced contractions by isoproterenol were antagonized by propranolol. The results in this report indicate that the effects elicited by acetylcholine and pilocarpine in pre-gill arterial vasculature of rainbow trout were mediated by muscarinic receptors. This study also presents evidence for the presence of both α- and β-adrenoceptors in ventral aorta of rainbow trout.

Pharmacology of the Placenta

A number of drugs, if administered during pregnancy, have the potential of increasing or decreasing the blood supply to the developing fetus via a variety of mechanisms. Two aspects of placental pharmacology are considered here: the capacity of the placenta to catalyze the biotransformation of xenobiotic (drug) substrates, and the effects of drugs on the placental vasculature.

Comparative effects of stereoisomers of psychotomimetic phenylisopropylamines

Abstract Stereoisomers, R(−) and S(+), of five psychotomimetic phenyliso-propylamines contracted isolated strips of sheep umbilical arteries. The compounds exhibited the following order of potency: 2,5-dimethoxy-4-bromo-amphetamine (DOB) > 2,5-dimethoxy-4-ethyl-amphetamine DOET) > 2,5-dimethoxy-4-methyl-amphetamine (DOM) > 2,5-dimethoxy-amphetamine (2,5-DMA) > 4-methoxy-amphetamine (PMA). Stereoselectivity was observed in that the R(−) isomers were more active than the S(+) isomers except for PMA. Evidence was obtained for the action of these hallucinogens on 5-hydroxytryptamine receptors. There was a general correlation of smooth muscle stimulating activity with known hallucinogenic activity.

Responses of isolated human uterine arteries to vasoactive drugs

Abstract Isolated human uterine arteries were found to respond to several clinically important vasoactive drugs, i.e., l-isoproterenol, l-norepinephrine, nitroglycerin, and angiotensinamide (angiotensin). Human uterine arteries possess alpha and beta adrenergic receptors. The contractile potency of norepinephrine was greater than that of angiotensin. Tachyphylaxis occurred with the use of angiotensin. The reliability of isolated human uterine arteries was quite good, which suggests that it might serve as a model for the examination of the actions of drugs on human vascular tissue.

Responses of guinea pig umbilical vasculature to vasoactive drugs

Abstract Isolated guinea pig umbilical arteries contracted in the presence of 5-hydroxytryptamine, norepinephrine, histamine, angiotensin, bradykinin and acetylcholine. The maximal contractions of the arteries to acetylcholine, norepinephrine and angiotensin were respectively 57,68 and 83% of the 5-hydroxytryptamine control; whereas, contractions to 5-hydroxytryptamine and bradykinin were similar. Maximal contractions to histamine were 173% of those to 5-hydroxytryptamine, but the concentration sufficient to produce a threshold contraction was tenfold greater for histamine. Differences between the response of the artery and vein to the various agonists were minimal. Evidence was obtained for the presence of both α- and β-adrenergic receptors. Responses to 5-hydroxytryptamine were mediated via D-receptors in that contractions were blocked by phenoxybenzamine and 2-bromolysergic acid diethylamide and not by cocaine or atropine. Contractions to 5-hydroxytryptamine and norepinephrine were potentiated in the presence of cocaine. In view of the lack of innervation in these blood vessels, the potentiation by cocaine must be brought about by a mechanism other than by an inhibition of amine uptake at a neuronal membrane site.

Comparative actions of selected vasoactive drugs on isolated human uterine arteries

Abstract Isolated human uterine arteries contracted to the following drugs in decreasing order of potency: norepinephrine, vasopressin, serotonin, histamine, ergonovine, and lysergic acid diethylamide. Oxytocin relaxed norepinephrine-contracted uterine arteries. Responses to serotonin were antagonized by methysergide, and those to histamine were antagonized by tripelennamine.

The action of vasopressors on isolated uterine arteries.

Abstract Isolated uterine arteries from nonpregnant human uteri and pregnant sheep uteri responded in a similar manner to 7 vasopressor drugs. Epinephrine and norepinephrine were equal in vasoconstrictor activity and about 10 times more active than phenylephrine and metaraminol which were also equally active. Ephedrine, mephentermine, and dopamine produced contractions of uterine arteries but only at high concentrations. Neither halothane (0.45 to 0.50 per cent), nitrous oxide (70 per cent), nor lidocaine (3 μg per milliliter) altered contractions to epinephrine or norepinephrine.

d-Lysergic acid diethylamide (LSD-25): A constrictor of human umbilical vein

Abstract In summary, experiments on isolated human umbilical vein indicated both serotonin and LSD-25 to be potent vasoconstrictors. The contractile response to LSD-25 was more persistent than to serotonin. In the lower concentration range, which may be more important clinically, LSD-25 was more potent than serotonin. In view of the current abuse of LSD-25, the results of our study may hint to possible toxic effects of LSD-25 on the fetus in utero. Our hypothesis is that upon crossing the placental barrier into the fetal circulation, LSD-25 could constrict the umbilical blood vessels. The constriction would result in a decreased fetal blood flow through the placenta which may cause fetal hypoxia and its potentially harmful consequences.

Prostaglandin E2 and its antagonists: Effects on autonomic transmission in the isolated sino-atrial node*

Abstract Prostaglandin E2 (PGE2) and its antagonists were tested for their effects on the chronotropic responses induced by electrical stimulation of autonomic nerve fibers in the isolated, spontaneously beating, rabbit sino-atrial node. PGE2 (8 × 10−7M) almost completely blocked positive chronotropic responses induced by stimulation of intrandal sympathetic fibers at low frequencies (2 – 5 Hz), while it had no effect at high frequencies of stimulation (20 – 100 Hz). Negative chronotropic responses induced by stimulation of intranodal parasympathetic fibers were only slightly and insignificantly reduced by PGE2 at low frequencies (2 – 20 Hz), and were increased at high frequencies (50 – 100 Hz). Three prostaglandin antagonists, polyphloretin phosphate (PPP), 7-oxa-13-prostynoic acid (EC-I-148) and 1-acetyl-2-(8-chloro-10,11-dihydrodibenz(b,f)(1,4)oxazepine-10-carbonyl) hydrazine (SC-19220), failed to antagonize the inhibitory effects of PGE2 on the chronotropic response induced by stimulation of intranodal fibers in the isolated sino-atrial node.